Global hyperperfusion after successful endovascular thrombectomy is linked to worse outcome in acute ischemic stroke.

Patients with stroke may develop hyperperfusion after a successful endovascular thrombectomy (EVT). However, the relationship between post-EVT hyperperfusion and clinical outcomes remains unclear and requires further clarification. We reviewed consecutive patients with anterior circulation occlusion who were successfully recanalized with EVT. Based on post-EVT arterial spin-labeling images, hyperperfusion was categorized as follows: global hyperperfusion (GHP), increased cerebral blood flow (CBF) in ≥ 50% of the culprit vessel territory; focal hyperperfusion (FHP), increased CBF in < 50% of the culprit vessel territory; no hyperperfusion (NHP), no discernible CBF increase. Factors associated with hyperperfusion were assessed, and clinical outcomes were compared among patients under different hyperperfusion categories. Among 131 patients, 25 and 40 patients developed GHP and FHP, respectively. Compared to other groups, the GHP group had worse National Institutes of Health Stroke Scale score (GHP vs. NHP/FHP, 18.1 ± 7.4 vs. 12.3 ± 6.0; p < 0.001), a larger post-EVT infarct volume (98.9 [42.3-132.7] vs. 13.5 [5.0-34.1] mL; p < 0.001), and a worse 90-day outcome (modified Rankin Scale, 3 [1-4] vs. 2 [0-3]; p = 0.030). GHP was independently associated with infarct volume (B = 0.532, standard error = 0.163, p = 0.001), and infarct volume was a major mediator of the association of GHP with unfavorable outcomes (total effect: ß = 0.176, p = 0.034; direct effect: ß = 0.045, p = 0.64; indirect effect: ß = 0.132, p = 0.017). Patients presenting with post-EVT GHP had poorer neurological prognosis, which is likely mediated by a large infarct volume.

Regional Disparities in Prehospital Delay of Acute Ischemic Stroke: The Korean Stroke Registry.

BACKGROUND: Late hospital arrival keeps patients with stroke from receiving recanalization therapy and is associated with poor outcomes. This study used a nationwide acute stroke registry to investigate the trends and regional disparities in prehospital delay and analyze the significant factors associated with late arrivals. METHODS: Patients with acute ischemic stroke or transient ischemic attack between January 2012 and December 2021 were included. The prehospital delay was identified, and its regional disparity was evaluated using the Gini coefficient for nine administrative regions. Multivariate models were used to identify factors significantly associated with prehospital delays of >4.5 h. RESULTS: A total of 144,014 patients from 61 hospitals were included. The median prehospital delay was 460 min (interquartile range, 116-1912), and only 36.8% of patients arrived at hospitals within 4.5 h. Long prehospital delays and high regional inequality (Gini coefficient > 0.3) persisted throughout the observation period. After adjusting for confounders, age > 65 years old (adjusted odds ratio [aOR] = 1.23; 95% confidence interval [CI], 1.19-1.27), female sex (aOR = 1.09; 95% CI, 1.05-1.13), hypertension (aOR = 1.12; 95% CI, 1.08-1.16), diabetes mellitus (aOR = 1.38; 95% CI, 1.33-1.43), smoking (aOR = 1.15, 95% CI, 1.11-1.20), premorbid disability (aOR = 1.44; 95% CI, 1.37-1.52), and mild stroke severity (aOR = 1.55; 95% CI, 1.50-1.61) were found to independently predict prehospital delays of >4.5 h. CONCLUSION: Prehospital delays were lengthy and had not improved in Korea, and there was a high regional disparity. To overcome these inequalities, a deeper understanding of regional characteristics and further research is warranted to address the vulnerabilities identified.

Blood urea nitrogen to albumin ratio is associated with cerebral small vessel diseases.

Blood urea nitrogen (BUN) to albumin ratio (BAR) is a comprehensive parameter that reflects renal, inflammatory, nutritional, and endothelial functions. BAR has been shown to be associated with various cancers, pneumonia, sepsis, and pulmonary and cardiovascular diseases; however, few studies have been conducted on its association with cerebrovascular diseases. In this study, we evaluated the association between BAR and cerebral small vessel disease (cSVD) in health check-up participants. We assessed consecutive health check-up participants between January 2006 and December 2013. For the cSVD subtype, we quantitatively measured the volume of white matter hyperintensity (WMH) and qualitatively measured the presence of lacune and cerebral microbleeds (CMBs). The BAR was calculated by dividing BUN by albumin as follows: BAR = BUN (mg/dl)/albumin (g/dl). A total of 3012 participants were evaluated. In multivariable linear regression analysis, BAR showed a statistically significant association with WMH volume after adjusting for confounders [ß = 0.076, 95% confidence interval (CI): 0.027-0.125]. In multivariable logistic regression analyses, BAR was significantly associated with lacunes [adjusted odds ratio (aOR) = 1.20, 95% CI: 1.00-1.44] and CMBs (aOR = 1.28, 95% CI: 1.06-1.55). BAR was associated with all types of cSVD in the health check-up participants.

Monocyte to high-density lipoprotein cholesterol ratio is associated with cerebral small vessel diseases.

BACKGROUND: Inflammation is a major pathological mechanism underlying cerebrovascular disease. Recently, a new inflammatory marker based on the ratio between monocyte count and high-density lipoprotein (HDL) cholesterol has been proposed. In this study, we evaluated the relationship between monocyte-to-HDL cholesterol ratio (MHR) and cerebral small vessel disease (cSVD) lesions in health check-up participants. METHODS: This study was a retrospective cross-sectional study based on a registry that prospectively collected health check-up participants between 2006 and 2013. Three cSVD subtypes were measured on brain magnetic resonance imaging. White matter hyperintensity (WMH) volume, and lacunes and cerebral microbleeds (CMBs) were quantitatively and qualitatively measured, respectively. The MHR was calculated according to the following formula: MHR = monocyte counts (× 103/µL) / HDL cholesterol (mmol/L). RESULTS: In total, 3,144 participants were evaluated (mean age: 56 years, male sex: 53.9%). In multivariable analyzes adjusting for confounders, MHR was significantly associated with WMH volume [ß = 0.099, 95% confidence interval (CI) = 0.025 to 0.174], lacune [adjusted odds ratio (aOR) = 1.43, 95% CI = 1.07-1.91], and CMB (aOR = 1.51, 95% CI = 1.03-2.19). In addition, MHR showed a positive quantitative relationship with cSVD burden across all three subtypes: WMH (P < 0.001), lacunes (P < 0.001), and CMBs (P < 0.001). CONCLUSIONS: High MHR was closely associated with cSVD in health check-up participants. Because these associations appear across all cSVD subtypes, inflammation appears to be a major pathological mechanism in the development of various cSVDs.

Targeted Metabolomic Biomarkers for Stroke Subtyping.

BACKGROUND AND PURPOSE: Ischemic stroke is a heterogeneous disease with various etiologies. The current subtyping process is complicated, time-consuming, and costly. Metabolite-based biomarkers have the potential to improve classification and deliver optimal treatments. We here aimed to identify novel, targeted metabolomics-based biomarkers to discriminate between large-artery atherosclerosis (LAA) and cardioembolic (CE) stroke. METHODS: We acquired serum samples and clinical data from a hospital-based acute stroke registry (ischemic stroke within 3 days from symptom onset). We included 346 participants (169 LAA, 147 CE, and 30 healthy older adults) and divided them into training and test sets. Targeted metabolomic analysis was performed using quantitative and quality-controlled liquid chromatography with tandem mass spectrometry. A multivariate regression model using metabolomic signatures was created that could independently distinguish between LAA and CE strokes. RESULTS: The training set (n = 193) identified metabolomic signatures that were different in patients with LAA and CE strokes. Six metabolomic biomarkers, i.e., lysine, serine, threonine, kynurenine, putrescine, and lysophosphatidylcholine acyl C16:0, could discriminate between LAA and CE stroke after adjusting for sex, age, body mass index, stroke severity, and comorbidities. The enhanced diagnostic power of key metabolite combinations for discriminating between LAA and CE stroke was validated using the test set (n = 123). CONCLUSIONS: We observed significant differences in metabolite profiles in LAA and CE strokes. Targeted metabolomics may provide enhanced diagnostic yield for stroke subtypes. The pathophysiological pathways of the identified metabolites should be explored in future studies.

Association of high-estimated glomerular filtration rate with the severity of ischemic stroke during non-vitamin K antagonist oral anticoagulants therapy: a nationwide cohort study.

Aim: While the relationship between impaired kidney function and non-vitamin K antagonist oral anticoagulants (NOACs) is well established, there is limited research exploring the association between an elevated estimated glomerular filtration rate (eGFR) and the efficacy of NOACs, especially concerning the outcomes of acute ischemic stroke (AIS). This study aimed to examine the association between higher-than-normal eGFR and the severity of AIS during the use of NOACs using a nationwide multicenter stroke registry in Korea. Material and methods: This study utilized data from the Korean Stroke Registry (KSR) database, examining information from 2,379 patients with AIS, who had atrial fibrillation (AF) and a history of utilizing NOACs prior to hospitalization due to incident stroke occurring between 2016 and 2021. Patients with a history involving two or more types of anticoagulants or one or more forms of antiplatelet agents were excluded. Baseline characteristics, medical history, medication usage, CHADS2-VASc score, and the anticoagulation and risk factors in atrial fibrillation (ATRIA) score were evaluated. Renal function was assessed using eGFR levels and calculated with the Cockcroft-Gault equation. The severity of stroke was measured by the National Institutes of Health Stroke Scale as an outcome. For sensitivity analysis, further evaluation was performed using eGFR levels according to the modification of diet in renal disease (MDRD) study equation. Results: The mean age of subjects was 76.1 ± 8.9 years. The moderate-to-severe stroke severity group exhibited an elevation in creatinine levels. The eGFR of 60 to 89 mL/min/1.73 m2 group was associated with a decreased risk of moderate-to-severe stroke severity [hazard ratio (HR)] (0.77, 95% confidence interval (CI) [0.61, 0.98], p = 0.031) compared to the eGFR≥90 mL/min/1.73 m2 group. An increment of 10 units in eGFR was marginally associated with an increased risk of moderate-to-severe stroke severity (HR: 1.03, 95% CI [1.00, 1.07], p = 0.054). Conclusion: The study revealed that individuals with eGFR ≥ 90 mL/min/1.73 m2 had an association linked to an increased risk of moderate-to-severe stroke severity. Our study suggests that patients taking NOACs with higher-than-normal eGFR levels may have an increased severity of AIS.

Clonal Hematopoiesis and Acute Ischemic Stroke Outcomes.

OBJECTIVE: The effect of clonal hematopoiesis of indeterminate potential (CHIP) on the manifestation and clinical outcomes of acute ischemic stroke (AIS) has not been fully elucidated. METHODS: Patients with AIS were included from a prospective registry coupled with a DNA repository. Targeted next-generation sequencing on 25 genes that are frequently mutated in hematologic neoplasms was performed. The prevalence of CHIP was compared between patients with AIS and age-matched healthy individuals. A multivariate linear or logistic regression model was used to assess the association among CHIP and stroke severity, hemorrhagic transformation, and functional outcome at 90 days. RESULTS: In total, 380 patients with AIS (mean age = 67.2 ± 12.7 years; 41.3% women) and 446 age-matched controls (mean age = 67.2 ± 8.7 years; 31.4% women) were analyzed. The prevalence of CHIP was significantly higher in patients with AIS than in the healthy controls (29.0 vs 22.0%, with variant allele frequencies of 1.5%, p = 0.024). PPM1D was found to be most significantly associated with incident AIS (adjusted odds ratio [aOR] = 7.85, 95% confidence interval [CI] = 1.83-33.63, p = 0.006). The presence of CHIP was significantly associated with the initial National Institutes of Health Stroke Scale (NIHSS) score (ß = 1.67, p = 0.022). Furthermore, CHIP was independently associated with the occurrence of hemorrhagic transformation (65/110 clonal hematopoiesis positive [CH+] vs 56/270 CH negative [CH-], aOR = 5.63, 95% CI = 3.24-9.77, p < 0.001) and 90-day functional disability (72/110 [CH+] vs 99/270 [CH-], aOR = 2.15, 95% CI = 1.20-3.88, p = 0.011). INTERPRETATION: CH was significantly associated with incident AIS. Moreover, particularly, sequence variations in PPM1D, TET2, and DNMT3A represent a new prognostic factor for AIS. ANN NEUROL 2023;94:836-847.

Presence of Embolic Source and Outcome in Central Retinal Artery Occlusion.

OBJECTIVES: The etiology of central retinal artery occlusion (CRAO) is unclear in approximately 50% of patients, suggesting pathomechanical heterogeneity; moreover, little is known about outcomes according to etiology. This study investigated whether the presence of an embolic source affects outcome in CRAO. METHODS: CRAO patients within 7 days of symptom onset were retrospectively enrolled. Clinical parameters, including initial and 1-month visual acuity, CRAO subtype, and brain images, were reviewed. CRAO etiology was categorized as CRAO with or without an embolic source (CRAO-E+ and CRAO-E-). Visual improvement was defined as a decrease in logarithm of the minimum angle of resolution ≥0.3 at 1 month. RESULTS: A total of 114 patients with CRAO were included. Visual improvement was noted in 40.4% of patients. Embolic sources were identified in 55.3% of patients, and visual improvement group rather than no improvement group was more commonly associated with the presence of an embolic source. In multivariable logistic regression analysis, CRAO-E+ independently predicted visual improvement (odds ratio 3.00, 95% CI 1.15-7.81, p = 0.025). DISCUSSION: CRAO-E+ was found to be associated with a better outcome. CRAO-E+ may be more prone to recanalization than that CRAO-E-.

Characteristics and Clinical Implication of White Matter Lesions in Patients With Adult Moyamoya Disease.

BACKGROUND AND OBJECTIVES: White matter hyperintensities (WMHs) are reportedly increased in moyamoya disease (MMD); however, their clinical importance is not well-established owing to their pathophysiologic heterogeneity by distribution. This study aimed to evaluate the burden and pattern of WMHs and its clinical implications in the MMD trajectory. METHODS: Adult patients with MMD without significant structural lesions were 1:1 propensity score-matched with healthy controls for sex and vascular risk factors. The total, periventricular, and subcortical WMH volumes were segmented and quantified fully automatically. WMH volumes were detrended by age and compared between the 2 groups. MMD severity based on Suzuki stage and future ischemic events were assessed for their association with WMH volumes. RESULTS: A total of 161 pairs of patients with MMD and controls were analyzed. MMD significantly correlated with increased total WMH volume (B [standard error], 0.126 [0.030]; p < 0.001), periventricular WMH volume (0.114 [0.027]; p < 0.001), and periventricular-to-subcortical ratio (0.090 [0.034]; p = 0.009). In the MMD subgroup (n = 187), advanced MMD had an independent association with the total WMH volume (0.120 [0.035]; p < 0.001), periventricular WMH volume (0.110 [0.031]; p < 0.001), and periventricular-to-subcortical ratio (0.139 [0.038]; p < 0.001). Periventricular WMH volume (adjusted hazard ratio [95% confidence interval], 5.12 [1.26-20.79]) and periventricular-to-subcortical ratio (3.80 [1.51-9.56]) were associated with future ischemic events in patients with medically followed up MMD. However, no demonstrable association was found between subcortical WMH volume and MMD, MMD severity, or future ischemic events. DISCUSSION: Periventricular WMHs, but not subcortical WMHs, may represent the main pathophysiology of MMD. Periventricular WMHs may be used as a marker for ischemic vulnerability in patients with MMD.

Association of Body Shape Index with Cerebral Small Vessel Disease.

INTRODUCTION: A body shape index (ABSI) is an anthropometric index designed to reflect the influence of visceral fat. ABSI has been previously associated with various atherosclerosis, metabolic diseases, and cardiovascular diseases; however, relatively few studies have been conducted on cerebrovascular disease. In this study, we evaluated the association between ABSI and cerebral small vessel disease (cSVD) in health check-up participants. METHODS: We evaluated consecutive health check-up participants between January 2006 and December 2013. As subtypes of cSVD, we quantitatively measured the volume of white matter hyperintensity (WMH) and qualitatively measured the presence of silent brain infarct (SBI) and cerebral microbleed (CMB). ABSI was calculated according to the following formula: ABSI (m11/6/kg-2/3) = waist circumference (m)/(body mass index [kg/m2]2/3 × height [m]1/2). RESULTS: A total of 3,219 health check-up participants were assessed (median age, 56 years; male sex, 54.0%). In the multivariable analysis, ABSI was significantly associated with WMH volume (ß = 0.107, 95% confidence interval [CI] = 0.013-0.200), SBI (adjusted odds ratio [aOR] = 1.62, 95% CI = 1.14-2.31), and CMB (aOR = 1.64, 95% CI = 1.16-2.33) after adjusting for confounders (per 100 m11/6/kg-2/3). Furthermore, ABSI showed a dose-response relationship with the burden of each cSVD pathology. CONCLUSIONS: High ABSI was associated with a higher burden of cSVD in health check-up participants. As ABSI showed close associations with all subtypes of cSVD, visceral fat may be a common risk factor penetrating cSVD pathologies.

Serum C3 complement levels predict prognosis and monitor disease activity in Guillain-Barré syndrome.

OBJECTIVE: Biomarkers are needed to predict prognosis and disease activity in patients with Guillain-Barré syndrome (GBS). The complement system is a key player in the pathogenesis of GBS. This study aimed to assess the potential utility of serum complement proteins as novel biomarkers in GBS. METHODS: We reviewed the medical records of 76 GBS patients with C3 and C4 measurements during hospitalization between 2010 and 2021. Clinical outcomes were correlated with baseline serum C3, C4, and seven additional predictors: four existing biomarkers (GM1, albumin, immunoglobulin G, neutrophil-lymphocyte ratio) and three clinical factors from the modified Erasmus GBS outcome score model. Five complement activation products (C3a, C4a, C5a, soluble C5b-9, factor Bb) were measured in 35 patients and were compared with C3 and C4 levels. Longitudinal changes in C3 and C4 levels were compared with the disease course in 12 patients. RESULTS: Higher C3, but not C4, was associated with poorer outcomes: lower Medical Research Council sum scores (MRCSS), higher GBS disability score (GBSDS), longer hospitalization, and more frequent treatment-related fluctuations. Age, MRCSS at admission, and baseline serum C3 were significant independent indicators of 1- and 3-month GBSDS. We found that C3 was positively correlated with C3a (r = 0.32) and C5a (r = 0.37), which indicates an activated complement cascade with high C3. Longitudinal change of C3 coincided with clinical severity of the disease course. INTERPRETATION: This study highlights the use of serum C3 as a novel mechanistic biomarker in GBS. Larger prospective studies are needed to validate our findings.

Annual exposure to PM10 is related to cerebral small vessel disease in general adult population.

Ambient air pollution is one of the most important global health issues. Although several studies have been reported the associations between air pollution and brain function or structure, impact of the air pollution on cerebral small vessel disease (cSVD) have rarely been explored in Asian adult population. We evaluated the association between exposure to air pollutants and cSVD in Korean asymptomatic adults. This cross-sectional study included 3257 participants of a health screening program from January 2006 to December 2013. All participants performed brain magnetic resonance imaging. To assess the cSVD, we considered three features such as white matter hyperintensities (WMH), silent lacunar infarction (SLI), and cerebral microbleeds (CMBs). The annual average exposure to air pollutants [particulate matter ≤ 10 µm in aerodynamic diameter (PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2), and carbon monoxide (CO)] was generated. The mean [standard deviation (SD)] age of the total 3257 participants was 56.5 (9.5) years, and 54.0% of them were male. Among all the included participants, 273 (8.4%) had SLI and 135 (4.1%) had CMBs. The mean volume (± SD) of WMH was 2.72 ± 6.57 mL. In result of linear regression analysis, the volume of WMH was associated with various potential factors including age, height, weight, smoking and alcohol consumption status, blood pressure (BP), hypertension, and diabetes mellitus. SLI-positive group, compared to the SLI-negative group, was older, shorter, and had higher BP as well as higher frequency of hypertension and diabetes mellitus. After adjusting for covariates, the annual average concentration of PM10 was significantly associated with the volume of WMH [ß (95% CI) for Model 1 = 0.082 (0.038- 0.125), p < 0.001; ß (95% CI) for Model 2 = 0.060 (0.013, 0.107), p = 0.013]. CMBs were not associated with the annual average concentration of PM10. No significant associations of NO2, SO2, and CO with cSVD were observed. In conclusion, PM10 exposure is associated with significant increases in brain WMH' volume and silent lacunar infarcts in asymptomatic adults.

Systemic immune-inflammation index is associated with white matter hyperintensity volume.

Systemic immune-inflammation index (SII) is a novel inflammatory marker based on the composition ratio of blood cell counts. In this study, we evaluated the association between the SII and cerebral small vessel disease (cSVD) in health check-up participants. We evaluated participants from our health check-up registry between 2006 and 2013. The SII was calculated using the following formula: SII = (platelet count × neutrophil count)/lymphocyte count. cSVD was assessed by considering white matter hyperintensity (WMH) volume, lacunes, and cerebral microbleeds (CMBs). A total of 3187 participants were assessed. In multivariable linear regression analysis, the SII was significantly related to WMH volume [ß = 0.120, 95% confidence interval (CI) 0.050-0.189]. However, lacunes and CMBs showed no statistical significance with the SII. In the subgroup analysis by age, the SII was significantly associated with WMH volume only in participants aged ≥ 60 years (ß = 0.225, 95% CI 0.068-0.381). In conclusion, a high SII was associated with cSVD. Since this association was more pronounced in WMH than in lacunes or CMBs, WMH might be closer to the inflammation-related pathological mechanisms.

Clinical Differences Between Stroke and Stroke Mimics in Code Stroke Patients.

BACKGROUND: The code stroke system is designed to identify stroke patients who may benefit from reperfusion therapy. It is essential for emergency physicians to rapidly distinguish true strokes from stroke mimics to activate code stroke. This study aimed to investigate the clinical and neurological characteristics that can be used to differentiate between stroke and stroke mimics in the emergency department (ED). METHODS: We conducted a retrospective observational study of code stroke patients in the ED from January to December 2019. The baseline characteristics and the clinical and neurological features of stroke mimics were compared with those of strokes. RESULTS: A total of 409 code stroke patients presented to the ED, and 125 (31%) were diagnosed with stroke mimics. The common stroke mimics were seizures (21.7%), drug toxicity (12.0%), metabolic disorders (11.2%), brain tumors (8.8%), and peripheral vertigo (7.2%). The independent predictors of stroke mimics were psychiatric disorders, dizziness, altered mental status, and seizure-like movements, while current smoking, elevated systolic blood pressure, atrial fibrillation on the initial electrocardiogram, hemiparesis as a symptom, and facial palsy as a sign suggested a stroke. In addition, the likelihood of a stroke in code stroke patients tended to increase as the number of accompanying deficits increased from the following set of seven focal neurological deficits: hemiparesis (or upper limb monoparesis), unilateral limb sensory change, facial palsy, dysarthria, aphasia (or neglect), visual field defect, and oculomotor disorder (P < 0.001). CONCLUSION: Some clinical and neurological characteristics have been identified to help differentiate stroke mimics from true stroke. In particular, the likelihood of stroke tended to increase as the number of accompanying focal neurological deficits increased.

Changes in Stroke Patients' Health-Seeking Behavior by COVID-19 Epidemic Regions: Data from the Korean Stroke Registry.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has led to changes in stroke patients' healthcare use. This study evaluated changes in Korean stroke patients' health-seeking behaviors and stroke care services using data from the Korean Stroke Registry (KSR). METHODS: We reviewed data from patients with acute stroke and transient ischemic attack (TIA) during 2019 (before COVID-19 period) and 2020 (COVID-19 period). Outcomes included patient characteristics, time from stroke onset to hospital arrival, and in-hospital stroke pathways. Subgroup analyses were performed for an epidemic region (Daegu city and Gyeongsangbuk-do region, the D-G region). RESULTS: The study included 1,792 patients from the pre-COVID-19 period and 1,555 patients from the COVID-19 period who visited hospitals that contribute to the KSR. During the COVID-19 period, the D-G region had two-thirds the number of cases (vs. the pre-CO-VID-19 period) and a significant decrease in the proportion of patients with TIA (9.97%-2.91%). Unlike other regions, the median onset-to-door time increased significantly in the D-G region (361 min vs. 526.5 min, p = 0.016), and longer onset-to-door times were common for patients with mild symptoms and who were in their 60s or 70s. The number of patients who underwent intravenous thrombolysis also decreased during the COVID-19 period, although the treatment times were not significantly different between the 2 periods. DISCUSSION/CONCLUSION: Korean stroke patients in a CO-VID-19 epidemic region exhibited distinct changes in health-seeking behaviors. Appropriate triage system and public education regarding the importance of early treatment are needed during the COVID-19 pandemic.

Current status and role of antiphospholipid antibody testing in cryptogenic stroke.

BACKGROUND AND PURPOSE: Although it is not recognized as essential to test for antiphospholipid antibody (aPL) in stroke of unknown cause, aPL-related stroke may account for a considerable number of cryptogenic strokes. We aimed to assess the current status and diagnostic value of aPL testing in cryptogenic stroke patients. METHODS: Consecutive patients admitted with acute ischemic stroke were examined to confirm the factors associated with performing aPL testing and with positive aPL test results in real-world practice. Cryptogenic stroke patients were separately examined in the same manner. The antibody profiles of cryptogenic stroke patients with aPL positivity were compared by age. RESULTS: Among 2947 patients, 606 (20.6%) were tested for aPLs and 129 (21.3%) were positive. Physicians tended to perform aPL testing in patients aged <50 years and in cryptogenic stroke patients. Cryptogenic stroke was a strong predictor of positive aPL results (adjusted odds ratio 3.70, 95% confidence interval 2.38-5.76). However, aPL positivity did not differ by age in stroke patients. Among 283 cryptogenic stroke patients, 136 (48.1%) were tested for aPLs and 56 (41.2%) were positive. aPL tests were performed predominantly in patients aged <50 years rather than in older patients, even among cryptogenic stroke patients. The two age groups had similar positivity rates of >40% (<50 years: 43.2%; ≥50 years: 40.4%; p = 0.92) and their antibody profiles were similar. CONCLUSIONS: A significant number of patients with cryptogenic stroke had positive aPL results regardless of age. aPL testing may offer additional diagnostic opportunities in cryptogenic stroke patients, and thus may reduce the incidence of cryptogenic stroke.

Renal Dysfunction Is Associated with Middle Cerebral Artery Pulsatility Index and Total Burden of Cerebral Small Vessel Disease.

BACKGROUND AND PURPOSE: Renal dysfunction is known to affect vasculature and lead to systemic arterial stiffness. It also independently increases the risk of cerebral small vessel disease (cSVD) and stroke. We aimed to examine the effect of renal dysfunction on cerebral hemodynamics and the burden of cSVD. METHODS: Of the 412 patients admitted to Seoul National University Hospital, between May 2015 and 2019, with lacunar infarction and no major intracranial arterial stenosis observed on magnetic resonance angiography, we included 283 patients who had undergone a transcranial Doppler (TCD) ultrasound after 72 h of stroke onset. The patients were divided into renal dysfunction (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m2 at admission) and control (eGFR ≥60 mL/min/1.73 m2) groups. We investigated the correlations between renal function, the pulsatility index (PI), and the total MRI burden of cSVD. Furthermore, multivariate analysis was performed to assess the association between renal dysfunction and the PI of the middle cerebral artery (MCA) measured through TCD ultrasound. RESULTS: Among the total patients, 74 (26.1%) had renal dysfunction (eGFR <60 mL/min/1.73 m2 at admission). Patients with renal dysfunction were significantly older, showed higher pulse pressure, and had a higher prevalence of hypertension, diabetes mellitus, and coronary artery disease. Renal dysfunction was significantly associated with higher distal cerebrovascular flow resistance (median PI 1.12, interquartile range [IQR]: 0.85-1.57 vs. controls 0.84, IQR: 0.54-1.22; p < 0.001). Also, patients with renal dysfunction had a significantly higher total MRI burden of cSVD (median cSVD score 2, IQR: 1-3 vs. controls median score 1, IQR: 0-2; p < 0.001). There was an inverse proportional relationship between the PI and eGFR. Finally, multivariate analysis showed renal dysfunction (adjusted odds ratio: 4.516, 95% confidence interval: 1.051-20.292) and older age (adjusted odds ratio: 1.076, 95% confidence interval: 1.038-1.114) as independent predictors of a high PI. CONCLUSIONS: Renal dysfunction is independently associated with a high PI of MCA. Renal dysfunction leads to systemic arterial stiffness including stiffness in cerebral arteries, thus increasing the burden of cSVD. Therefore, noninvasive screening for high PI by TCD in kidney failure patients might be helpful.

Glycated Albumin, a Novel Biomarker for Short-Term Functional Outcomes in Acute Ischemic Stroke.

Background: There is growing interest in the use of new biomarkers such as glycated albumin (GA), but data are limited in acute ischemic stroke. We explored the impact of GA on short-term functional outcomes as measured using the modified Rankin Scale (mRS) at 3 months compared to glycated hemoglobin (HbA1c). Methods: A total of 1163 AIS patients from two hospitals between 2016 and 2019 were included. Patients were divided into two groups according to GA levels (GA < 16% versus GA ≥ 16%). Results: A total of 518 patients (44.5%) were included in the GA ≥ 16% group. After adjusting for multiple covariates, the higher GA group (GA ≥ 16%) had a 1.4-fold risk of having unfavorable mRS (95% CI 1.02-1.847). However, HbA1c was not significantly associated with 3-month mRS. In addition, GA ≥ 16% was independently associated with unfavorable short-term outcomes only in patients without diabetes. Conclusions: In light of these results, GA level might be a novel prognostic biomarker compared to HbA1c for short-term stroke outcome. Although the impact of GA is undervalued in the current stroke guidelines, GA monitoring should be considered in addition to HbA1c monitoring.